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Q&A: The growing threat of Klebsiella
In February, WHO released a list of antibiotic-resistant “priority pathogens,” identifying 12 families of bacteria that pose the greatest danger to human health.
The list, which is part of WHO’s efforts to encourage and steer new antibiotic research and development, was compiled in response to the mounting problem of resistance to antimicrobial agents across the globe.
The list emphasizes the threat posed by multidrug-resistant, gram-negative bacteria, which have the inherent adaptive ability to resist treatment and also pass along genetic material that facilitates drug resistance in other bacteria.
The list categorizes groups of bacteria based on the need for new antibiotics to combat them, designating the families of bacteria as “critical,” “high,” and “medium” priority.
The “critical” list includes multidrug-resistant bacteria groups that are prevalent in health care settings, such as hospitals and nursing homes. These bacteria are also particularly dangerous in patients who require devices such ventilators and blood catheters, according to WHO. These bacteria include Acinetobacter, Pseudomonas, and several carbapenem-resistant Enterobacteriaceae — a category of bacteria that, in 2013, the CDC called “nightmare bacteria.” Among the bacteria in this category are Klebsiella, microbes that cause the Klebsiella pneumoniae infection.
Recent research conducted at Queen’s University Belfast in Ireland found that in addition to being recalcitrant to treatment, Klebsiella appear to have the capacity to cause more serious infections by counteracting the body’s defenses. The lead investigator of this study, Jose A. Bengoechea, PhD, director of the university’s Centre for Experimental Medicine, spoke with Infectious Disease News about the increasing threat of Klebsiella, the dearth of new antibiotics to address it, and the frightening possibility of a “post-antibiotic era.” – by Jennifer Byrne
Klebsiella were some of the top microbes on the WHO’s “priority pathogens” list of the most threatening bacteria. What are your thoughts about this list, and about Klebsiella’s place on it?
By including Klebsiella pneumoniae as one of the top three microbes posing a threat to human health, WHO acknowledges the clinical problem faced in many hospitals worldwide. There is a significant increase in the percentage of Klebsiella resistant to at least three antibiotics. Furthermore, these multidrug-resistant Klebsiella are disseminated worldwide and in some settings cause outbreaks virtually impossible to treat due to the lack of treatments. Unfortunately, at present, we cannot identify candidate compounds in late-stage development for treatment of multidrug-resistant Klebsiella infections. Klebsiella are exemplary of the mismatch between unmet medical needs and the current antimicrobial research and development pipeline. The development of new antibiotics is slow and difficult work, but bacterial resistance is decreasing our arsenal of existing drugs. A post-antibiotic era — in which common infections and minor injuries can kill — is far from an apocalyptic fantasy. It’s a very real possibility for the 21st century, and Klebsiella infections are one of the major threats.
How can a “post-antibiotic era” be prevented?
Indeed, as has been already acknowledged by many stakeholders, we are running out of options to treat these infections. Alarmingly, there are no drugs in the pipeline that could enter into clinical use in the next 5 years. It is evident that there is an urgent need to support research to close this clinical gap as soon as possible. Furthermore, I believe it is important to support blue skies research to identify much needed new therapeutics.
On the other hand, and to mitigate this problem, it is important to correctly use antibiotics by strictly following GPs and doctors’ advice. Also, better diagnostic systems are crucially important, so we can start treatments earlier and use a targeted treatment. These measures will not tackle the problem but certainly will buy us time to develop new therapeutics.
Why do Klebsiella cause severe infections?
Despite the clinical relevance, there is still a significant gap in our understanding of why Klebsiella may cause severe infections. Recent studies indicate that Klebsiella can adapt to different environments and conditions, hence allowing the microbes to colonize and persist in many different environments (hospitals, the soil, animals). On my team, we have been investigating this topic during the last 10 years. The development of new therapeutic strategies requires a better understanding of K. pneumoniae pathophysiology in the context of the complex interactions between the microbe and our body. Perhaps one of our most important findings is the discovery that Klebsiella manipulate several pathways in our cells to prevent the activation of defense mechanisms. By building upon this knowledge platform, we are currently aiming to provide initial evidence demonstrating that therapeutic antagonism of this virulence strategy will favor Klebsiella clearance.
The incidence of hypervirulent K. pneumoniae has been increasing in certain regions, including China. How large of a problem is this globally?
It depends pretty much on the area, but already in the U.K. there has been a 12% increase in the number of invasive infections by this pathogen. These highly virulent Klebsiella strains are still not multidrug- resistant. However, it is becoming evident that this is changing. There are already reports of infections caused by virulent and antibiotic-resistant strains in the U.S., China and Europe. If these strains become distributed worldwide, we might be facing a “perfect storm”: a virulent microbe that is extremely difficult to treat.
What is the role of the clinician in the prevention of carbapenem-resistant Enterobacteriaceae, like Klebsiella spp.?
It is important to follow the guidelines and control as much as possible the use of wide-spectrum antibiotics carbapenem and colistin. Nonetheless, clinicians are indeed doing their best with the tools they have in place. However, it might be important to introduce available novel molecular approaches into our hospitals to avoid treatment delays while assessing the antimicrobial resistance pattern and the virulence profile of the infecting microbe.
Reference:
Li W, et al. Clin Infect Dis. 2013;doi:10.1093/cid/cit675.
Disclosure : Bengoechea reports receiving research support by the Biotechnology and Biological Sciences Research Council and the European Union (Marie Curie Career Integration Grant U-KARE).